Type I interferon associated epistasis may contribute to early disease-onset and high disease activity in juvenile-onset lupus.

Pathologic type I interferon (T1IFN) expression is a key feature in systemic lupus erythematosus (SLE) that associates with disease activity. When compared to adult-onset disease, juvenile-onset (j)SLE is characterized by increased disease activity and damage, which likely relates to increased genetic burden. To identify T1IFN-associated gene polymorphisms (TLR7, IRAK1, miR-3142/miR-146a, IRF5, IRF7, IFIH1, IRF8, TYK2, STAT4), identify long-range linkage disequilibrium and gene:gene interrelations, 319 jSLE patients were genotyped using panel sequencing. Coupling phenotypic quantitative trait loci (QTL) analysis identified 10 jSLE QTL that associated with young age at onset (<12 years; IRAK1 [rs1059702], TLR7 [rs3853839], IFIH1 [rs11891191, rs1990760, rs3747517], STAT4 [rs3021866], TYK2 [rs280501], IRF8 [rs1568391, rs6638]), global disease activity (SLEDAI-2 K >10; IFIH1 [rs1990760], STAT4 [rs3021866], IRF8 [rs903202, rs1568391, rs6638]), and mucocutaneous involvement (TLR7 [rs3853839], IFIH1 [rs11891191, rs1990760]). This study suggests T1IFN-associated polymorphisms and gene:gene interrelations in jSLE. Genotyping of jSLE patients may allow for individualized treatment and care.

Association of disease activity with depression and anxiety in systemic lupus erythematosus: A comparison of SLEDAI-2K and SLE-DAS.

OBJECTIVE: To explore the association of disease activity, as evaluated by both the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) and the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K), with depression and anxiety in patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted among 85 Chinese patients with SLE. Disease activity was measured using SLEDAI-2K and SLE-DAS scoring systems. Depression and anxiety were assessed using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Scale-7 (GAD-7), respectively. Multivariate logistic regression analysis was performed to evaluate the association of disease activity scores, as well as specific clinical and laboratory items, with depression and anxiety. RESULTS: There was a robust correlation between SLEDAI-2K and SLE-DAS scores in overall patients (Spearman's r = 0.764, 95% confidence interval (CI) 0.655-0.842; p< 0.001) and those with moderate-to-high disease activity (Spearman's r = 0.792, 95%CI 0.616-0.892; p< 0.0001). However, the correlation weakened for patients with mild disease activity or remission (Spearman's r = 0.450, 95%CI 0.188-0.652; p= 0.001). Multivariate logistic regression analysis did not show a significant correlation between SLEDAI-2K and SLE-DAS scores and depression/anxiety. The presence of mucosal ulcer/serositis significantly increased the risk of depression (OR = 4.472, 95%CI 1.035-19.328, p= 0.045) and anxiety (OR = 3.978, 95%CI 1.051-15.049, p= 0.042). CONCLUSION: The SLE-DAS scoring system demonstrated a comparable ability to assess disease activity in SLE compared with SLEDAI-2K. Though neither scoring system showed significant associations with depression and anxiety, the presence of mucosal ulcer/serositis markedly heightened the risk of both among SLE patients.

Comparisons of SLE-DAS and SLEDAI-2K and classification of disease activity based on the SLE-DAS with reference to patient-reported outcomes.

OBJECTIVES: Although the SLE Disease Activity Score (SLE-DAS) and its definitions to classify disease activity have been recently developed to overcome the drawbacks of the SLE Disease Activity Index 2000 (SLEDAI-2K), the performance of the SLE-DAS for patient-reported outcomes (PROs) has not been fully examined. We aimed to compare SLE-DAS with SLEDAI-2K and validate the classifications of disease activity based on SLE-DAS in terms of PROs. METHODS: We assessed generic quality of life (QoL) using the Medical Outcome Survey 36-Item Short-Form Health Survey (SF-36), disease-specific QoL using the lupus patient-reported outcome tool (LupusPRO), burden of symptoms using the SLE Symptom Checklist (SSC), patient global assessment (PtGA) and physician global assessment (PhGA). RESULTS: Of the 335 patients with SLE, the magnitudes of the mean absolute error, root mean square error, Akaike information criterion, and Bayesian information criterion were comparable for most PROs between the SLE-DAS and SLEDAI-2K. In contrast, SLEDAI-2K had a higher predictive value for health-related QoL of LupusPRO and PtGA than SLE-DAS. Low disease activity, Boolean and index-based remission and categories of disease activity (remission, mild and moderate/severe activity) were significantly associated with health-related QoL in LupusPRO, SSC and PhGA, but not SF-36 or PtGA. CONCLUSION: No clear differences were identified in the use of the SLE-DAS over the SLEDAI-2K in assessing PROs in patients with SLE. The classification of disease activity based on the SLE-DAS was validated against several PROs. SLE-DAS and its categories of disease activity effectively explain some of the PROs.

Serum pentraxin 3 in systemic lupus erythematosus: A potential indicator of cutaneous disease activity.

BACKGROUND: Although skin manifestations are common in systemic lupus erythematosus (SLE), there is still a lack of a diagnostic marker for cutaneous involvement. Pentraxin3 (PTX3) has been studied in SLE patients; however, it has not been investigated in relation to cutaneous manifestations. OBJECTIVE: To assess the serum PTX3 level in SLE patients, and to investigate its relationship with disease activity as well as with variable skin manifestations. PATIENTS AND METHODS: Thirty-four patients with SLE (17 patients with skin manifestations and 17 without) and 30 healthy subjects were included in the study. Patients were evaluated clinically for systemic and skin manifestations of SLE. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2k) and Cutaneous Lupus Erythematosus Activity and Severity Index (CLASI) scores were calculated. Serum level of PTX3 was measured in patients and controls using ELISA. RESULTS: Higher serum PTX3 level was found in SLE patients compared to controls (p < 0.001). Patients with skin manifestations showed higher SLEDAI-2k scores and had higher PTX3 level compared to those without skin manifestations (p = 0.015 and p < 0.001, respectively). PTX3 showed higher levels in association with malar rash (p < 0.001), mucosal ulcers (p < 0.001), alopecia (p < 0.001), and purpuric eruption (p = 0.002). Moreover, PTX3 level positively correlated with CLASI scores (p < 0.001). CONCLUSION: Our results reinforce the important role of Pentraxin3 in SLE patients with skin manifestations, and it may be considered an interesting biomarker for the pattern and extent of cutaneous involvement in SLE.

Increased frequency of hospital admissions with active systemic lupus erythematosus disease activity defined by two different disease activity indices: A cohort study.

The objective of this cohort study was to evaluate the association between the frequency of hospital admissions and disease activity, as defined by two different disease activity measurements: the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), in adult patients with systemic lupus erythematosus (SLEs). Patients with SLE were recruited from the rheumatology outpatient department of a regional hospital in southern Taiwan. SLE-DAS and SLEDAI-2K were used to define SLE disease activity and the cause of hospital admissions was identified by a rheumatologist based on medical records. A generalized linear model (GLM) with gamma distribution and log-linked function was used to analyze variables associated with the frequency of admission. The mean frequency of hospitalization was 0.34 times per year for all-cause and 0.21 times per year for SLE-related admission. Multivariate GLM analysis showed that moderate/severe SLE disease activity defined by SLE-DAS was associated with an increased frequency of all-cause and SLE-related hospital admissions while adjusting for other covariates. Moderate/severe SLE disease activity defined by SLEDAI-2K was only significantly associated with an increased frequency of all-cause hospitalization. When steroid dosage was included in the model, moderate/severe SLE disease activity defined by the SLE-DAS remained significantly associated with SLE-related hospital admissions (p = 0.032). In conclusion, disease activity defined by the SLE-DAS, but not SLEDAI-2K was associated with an increased frequency of SLE-related hospitalization. Steroid dosage, a lower educational level, and smoking were associated with an increased frequency of hospital admissions, whereas underweight and alcohol use were associated with a decreased frequency of hospital admissions. Rheumatologists should promptly control SLE disease activity of their patients, provide them with adequate health education, and maintain steroid doses to as low as possible to reduce the risk of hospital admissions.

BAFFR expression in circulating T follicular helper (CD4+CXCR5+PD-1+) and T peripheral helper (CD4+CXCR5-PD-1+) cells in systemic lupus erythematosus.

BACKGROUND: Circulating T follicular helper (cTfh) and T peripheral helper (Tph) subpopulations are shown to be higher in systemic lupus erythematosus (SLE) patients and have been involved in promoting extrafollicular B cell responses. However, a possible association with the B cell activating factor (BAFF), a cytokine mainly related to B cell responses and disease activity in SLE, has not been investigated. Therefore, this study aimed to evaluate the association of cTfh and Tph subpopulations with the BAFF system expression and clinical activity in SLE patients. METHODS: This study included 43 SLE patients and 12 healthy subjects (HS). The identification of cTfh (CD4+CXCR5+PD-1+), Tph (CD4+CXCR5-PD-1+) cells, expression of membrane-bound BAFF (mBAFF), BAFFR, TACI, BCMA, and intracellular IL-21 was performed by flow cytometry. Serum levels of IL-21, CXCL13, and BAFF were analyzed using ELISA. The SLEDAI-2K score was used to evaluate disease activity in SLE patients. RESULTS: Compared with HS, SLE patients showed a significantly increased percentage of cTfh and Tph cells, higher in patients with clearly active disease. SLE patients had markedly higher IL-21-producing cTfh and Tph cells than HS. Both subpopulations were positively correlated with the disease activity in SLE patients. Tph cells were negatively correlated with CD19+CXCR5+ B cells and positively correlated with CD19+CXCR5- B cells. A low expression of mBAFF and their receptors TACI and BCMA was found on cTfh and Tph cells in SLE patients and HS. However, SLE patients with clearly active disease showed decreased expression of BAFFR on cTfh and Tph subpopulations than patients with mildly active/nonactive disease. Serum IL-21, CXCL13, and BAFF levels were higher in SLE patients than in HS. Levels of CXCL13 were correlated with disease activity. Non-significant correlations were observed among T cell subpopulations and IL-21, CXCL13, and BAFF levels. CONCLUSIONS: This study emphasizes the importance of cTfh and Tph cells in SLE pathogenesis. Besides the importance of IL-21, our results suggest that BAFFR could play a role in cTfh and Tph subpopulations in the autoimmunity context.

Performance of a New Instrument for the Measurement of Systemic Lupus Erythematosus Disease Activity: The SLE-DAS.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that affects multiple organ systems and manifests in a relapsing-remitting pattern. Consequently, it is paramount for rheumatologists to assess disease activity, identify flare-ups, and establish treatment goals for patients with SLE. In 2019, the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) was introduced as a novel tool for measuring disease activity. This tool refines the parameters of the established SLE Disease Activity Index 2000 (SLEDAI-2K) to enhance the assessment process. This review aims to provide an introduction to the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) and summarizes research on its development, its comparison with existing disease activity measures, and its performance in clinical settings. Literature searches on PubMed using the keyword "SLE-DAS" were conducted, covering publications from March 2019 to September 2023. Studies that compared SLE-DAS with other SLE disease activity measurement tools were reviewed. Findings indicated that SLE-DAS consistently performs on par with, and sometimes better than, traditional measures in assessing clinically meaningful changes, patient improvement, disease activity, health-related quality of life, hospitalization rates, and disease flare-ups. The association between SLE-DAS and mortality rates among patients with SLE, however, remains to be further explored. Although SLE-DAS is a promising and potentially effective tool for measuring SLE disease activity, additional research is needed to confirm its effectiveness and broaden its clinical use.

A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus.

Upregulation of interferon-regulated genes (IRGs), denoted IFN signature, in peripheral blood has been used as an indirect measure of IFN pathway activation in patients with systemic lupus erythematosus (SLE). However, it has not been determined, which IFN signatures that optimally reflect clinical disease activity. In this study, we determined an IFN signature based on the expression of 128 IRGs in whole blood from 34 SLE patients in a cross-sectional (CS) study, 11 with active lupus nephritis followed longitudinally (LS) and 15 healthy controls. Blood samples were collected in PAXgene tubes and RNA was extracted and purified using a PAXgene blood RNA kit (Qiagen). Gene expression was measured using the NanoString nCounter Gene Expression platform. The CS SLE patients with higher disease activity displayed thrice as many upregulated IRGs (n = 46) as the rest. These IRGs clustered in three groups, consisting of IRGs known to be predominantly stimulated by type I (gene cluster K1) and type II (gene clusters K2 and 3) IFNs. SLEDAI-2K scores associated with the K2 and K3 gene scores (ß = 0.372 and ß = 0.419, both p < 0.015) but not with K1. In the longitudinal study, the mean SLEDAI-2K score decreased after an average follow-up of 360 days (ß = -2.08, P = 5.09 × 10-12). The mean K1, K2 and K3 gene scores did not change over time, however longitudinal changes in SLEDAI-2K and K3 scores were associated (ß = 0.814, p = 0.007). This study validates the presence of type I IRG subsets that do not associate with disease activity in SLE patients. The novel finding in this study is the association between a type II IRG subset and disease activity. Both findings may have significant implications for choosing IRGs defining clinically relevant IFN signatures.

The relation of CD4+CD25+Foxp3+ regulatory T cells concentration with disease activity and damage index in systemic lupus erythematosus.

INTRODUCTION: Regulatory T cells (Treg) deficits, both quantitative and qualitative, are known to be possible triggers for the development of autoimmune disorders by causing T and B cells dysfunction. The contribution of Treg deficiency in the etiology of systemic lupus erythematosus (SLE) is still being debated. The aim of the present study is to evaluate the percentage of circulating CD4+CD25+Foxp3+ Treg cells in a cohort of Egyptian SLE patients and to correlate this value with the activity and damage index of these patients. METHODS: 50 female patients with SLE together with an equal number of age- and sex-matched healthy controls were enrolled in the study. Flow cytometric determination of peripheral Treg cells was carried out for all participants by detecting the percentage of CD4+CD25+Foxp3+ cells to compare cases with the control group. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), while disease damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI). Both indices were correlated with the percentage of CD4+CD25+Foxp3 T regulatory cells. RESULTS: CD4+CD25+Foxp3+ Treg cells percentage was significantly decreased in patients with SLE as compared to healthy controls. On correlating CD4+CD25+Foxp3+ Treg percentage with SLEDAI-2K, a significantly negative correlation was found. Also, there was a negative significant correlation between CD4+CD25+Foxp3+ Treg cells percentage and SLICC/ACR DI. On correlating SLEDAI-2K with damage index (SLICC/ACR DI), we found highly significant positive correlation. CONCLUSION: Our study showed impaired production of CD4+CD25+Foxp3+ Tregs in SLE patients, which can play a reciprocal role with some cytokines to affect the activity of the disease and organ damage. CD4+CD25+Foxp3+ Tregs cells should be the target to determine the clinical effectiveness of new therapy to modulate Tregs besides the traditional treatments.

Cutaneous, systemic features and laboratory characteristics of late- versus adult-onset systemic lupus erythematosus in 1006 Thai patients.

BACKGROUND: Age at disease onset may modulate systemic lupus erythematosus (SLE), but its relation to cutaneous/extracutaneous manifestation remains understudied. OBJECTIVE: To compare the cutaneous, systemic features, laboratory characteristics, and disease severity between late- and adult-onset SLE patients. METHODS: Analyses of the cutaneous, systemic involvement, laboratory investigations, SLE disease activity index 2000 (SLEDAI-2K), and disease damage were performed to compare between groups. RESULTS: Of 1006 SLE patients, 740 and 226 had adult- (15-50 years) and late-onset (>50 years), respectively. Among 782 with cutaneous lupus erythematosus (CLE), acute CLE (ACLE) and chronic CLE (CCLE) were more common in the adult- and late-onset SLE, respectively (p = 0.001). Multivariable logistic regression analysis demonstrated that male patients and skin signs, including papulosquamous subacute CLE, discoid lupus erythematosus, and lupus profundus, were associated with late-onset SLE (all p < 0.05). Late-onset SLE had lower lupus-associated autoantibodies, and systemic involvement (all p < 0.05). ACLE, CCLE, mucosal lupus, alopecia, and non-specific lupus were related to higher disease activity in adult-onset SLE (all p < 0.001). There was no difference in the damage index between the two groups. CONCLUSIONS: Late-onset SLE had a distinct disease expression with male predominance, milder disease activity, and lower systemic involvement. Cutaneous manifestations may hold prognostic values for SLE.

Fatty acid binding protein 4 (FABP4) and metabolic-related parameters in systemic lupus erythematosus active and non-active episode.

OBJECTIVE: To assess serum FABP4 and other metabolic-related parameters in Systemic Lupus Erythematosus (SLE) active and non-active episode. METHODS: Fifty-four SLE patients in Hasan Sadikin General Hospital, Bandung, Indonesia in 2018-2019 were recruited and serum samples were collected in their active and non-active episode status. Serum was analyzed for FABP4, leptin, glucose, and triglycerides. The clinical characteristics were analyzed from medical records. Disease activity was assessed with the SLEDAI-2K (≥4 defined as an active; <4 as non-active episode). RESULTS: Significantly correlation of Systolic Blood Pressure (SBP) (p = 0.001, r = 0.59) and C3 (p = 0.04, r = 0.47) between active and non-active episode. In non-active episode, there was significant correlation of FABP4 with Diastolic Blood Pressure (DBP) (p = 0.04, r = 0.26) and blood glucose (p = 0.01, r = -0.39). In active episode, there was significant correlation FABP4 with SBP (p = 0.04, r = -0.28) and triglyceride (p = 0.002, r = 0.55). CONCLUSION: FABP4 correlates with high DBP in the non-active and high triglyceride serum in the active episode.

Cytokines, 25-OH vit D and disease activity in patients with juvenile-onset systemic lupus erythematosus.

BACKGROUND: Juvenile onset systemic lupus erythematosus JO-SLE patients usually exhibit a more aggressive disease course compared to adult patients. Vitamin D deficiency is proposed to be associated with increased disease activity and flares of numerous autoimmune diseases like SLE, rheumatoid arthritis, and scleroderma. OBJECTIVE: To evaluate the level of IL-17, IFN-γ, and 25-OH Vit D in JO-SLE patients versus healthy controls, and determine the correlation of those inflammatory mediators with SLE disease activity and damage scores. Furthermore, to analyze the relationship between 25-OH Vit D levels with the inflammatory cytokines (IFN-γ and IL-17) in JO-SLE patients. PATIENTS AND METHODS: Fifty JO-SLE patients and 25 controls were included in this study. Clinical and laboratory data of patients at the time of the study were recorded. SLE disease activity and damage were assessed using the SLEDAI-2K disease score and SLICC damage index, respectively. Plasma 25-OH Vit D, IFN-γ, and IL-17 concentrations were determined using the human ELISA kit. RESULTS: Plasma 25-OH Vit D levels (20 ng/mL) were significantly lower in JO-SLE patients compared to (31 ng/mL) controls (P = 0.014). Plasma levels of IFN-γ and IL-17 were significantly higher (163.5 and 25.5 pg./mL) in JO-SLE patients than (68.3 and 3 pg./mL) that of controls (P = 0.016 and P = 0.013). There was a significant negative correlation between 25-OH Vit D levels and SLEDAI-2K (R= -0.431) as well as IFN-γ (R= -0.471) plasma level (P = 0.022 and P = 0.027). CONCLUSION: IFN-γ and IL-17 were significantly higher in JO-SLE patients, while 25-OH Vit D was significantly lower compared to controls. There was a negative correlation between 25-OH Vit D and each of SLEDAI-2K and IFN-γ.

Septicaemia is associated with increased disease activity and mortality in systemic lupus erythematosus: a retrospective analysis from Taiwan.

OBJECTIVE: This study aimed to investigate how septicaemia, non-septicaemia infection and the disease itself are associated with disease activity and mortality in inpatients with systemic lupus erythematosus (SLE) in Taiwan. METHODS: We retrospectively reviewed 1115 patients and enrolled 427 with SLE admitted for lupus flare-ups and co-morbidities. Disease activity and infection type/site were recorded and categorized according to the causes of admission and mortality into three categories, of which two were specified as follows: (a) septicaemia admissions, non-septicaemia admissions; and (b) septicaemia mortality, non-septicaemia infection mortality and non-infection mortality. The relationships between lupus flare-ups and mortality in different groups were analysed using an unpaired t-test, Mann-Whitney U-test and logistic regression. RESULTS: Septicaemia was the major cause of mortality in SLE inpatients. There were 98 (22.95%) mortality patients among all 427 SLE patients. The septicaemia admissions had higher disease activity (SLE Disease Activity Index 2000 = 13.00 ± 7.98) than the non-septicaemia admissions (9.77 ± 5.72; p < 0.01). The mean current SLEDAI score of the septicaemia mortality group (14.91 ± 8.01) was higher than that of the non-septicaemia infection mortality group (10.05 ± 5.75; p = 0.02), in spite of the similar mean earlier SLEDAI score. The risk of mortality in the septicaemia mortality group due to previous septicaemia admissions was 13.2 times (odds ratio) higher than in the non-septicaemia infection mortality group and 15.6 times higher than in the non-infection mortality group. CONCLUSION: Septicaemia relates to increased lupus disease activity and is associated with a greater risk of mortality in the SLE patients than other causes of admission. Fewer previous septicaemia admissions decrease the risk of septicaemia mortality.

Urinary C3d is elevated in patients with active Lupus nephritis and a fall in its level after 3 months predicts response at 6 months on follow up.

INTRODUCTION: Complement activation is central to the pathogenesis of lupus nephritis (LN). Low serum complement C3 and C4, are traditionally used as markers of lupus disease activity in general and LN in particular. In this study we prospectively measured plasma and urine C3d and C4d, degradation products of C3 and C4 corrected to creatinine in a cohort of biopsy proven LN in a longitudinal fashion for its correlation with disease activity. METHODS: Twenty eight biopsy proven active lupus nephritis (AN) were recruited along with four inactive nephritis (IN) and 10 healthy controls (HC). Plasma and urine were collected at baseline, prior to induction treatment and 3 months later. Clinical measures of disease activity, Systemic lupus erythematosus disease activity index 2000 (SLEDAI 2K), renal SLEDAI, serum C3, C4 and antibodies to ds DNA, urine protein and creatinine excretion (UP/UC) were collected. Plasma and urine C3d and C4d were measured using ELISA and normalized to spot urine creatinine value. RESULTS: Twenty eight AN of median age of 26.5 (20-31.50) years and disease duration of 3 (0.7-5) years were enrolled. The median urinary C3d/creatinine before treatment was 388.20 (48.98-1296) ng/mg which fell significantly to 62.69 (28.04-502.4) ng/mg at 3 months followup (p-0.01). The baseline values for the active renal disease was significantly different from IN group (9.9 (4.5-46.53 ng/mg) p-0.00). Treatment responders (partial and complete) at 6 months showed a significant fall in urinary C3d at 3 months whereas non responders had a non significant change in value. There was a significant correlation of urine C3d/creatinine with SLEDAI2K (r-0.433, p-0.00), renal SLEDAI (r-0.356, p-0.00), UP/UC ratio (r-0.489, p-<0.0001) but no significant correlation with C3 or C4. There was a significant fall in the median values of plasma C3d from 791.1 (516.0.00-1550.43) µg/ml to 338.52 (211.35-525.82) (p-0.00) µg/ml at the end of 3 months. The values showed a significant correlation with SLEDAI 2K, renal SLEDAI, UP/UC along with a significant negative correlation with C3 and C4. CONCLUSION: Urinary C3d/creatinine levels and plasma C3d levels can be used as biomarker of disease activity and treatment response.

Changes in the result of antinuclear antibody immunofluorescence assay on HEp-2 cells reflect disease activity status in systemic lupus erythematosus.

Background The objective of the study was to determine whether the staining pattern and titer of indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) are associated with systemic lupus erythematosus (SLE) disease activity. Methods A total of 269 consecutive patients meeting the ACR and SLICC criteria for SLE were classified into three groups according to the SLE Disease Activity Index 2000 (SLEDAI2K): Remission (SLEDAI2K = 0; n = 47); Intermediate (SLEDAI2K = 1-5; n = 111); Active (SLEDAI2K ≥ 6; n = 111). All subjects were assessed for HEp-2 IFA titer and staining pattern and nine traditional parameters of SLE disease activity. After a 6 to 12-month interval, 101 of the 269 patients were reassessed. Results HEp-2 IFA homogeneous nuclear pattern (AC-1) occurred more frequently in the Active Group compared to the Remission Group (p < 0.001). Fine speckled nuclear pattern (AC-4) tended to occur more frequently in the Remission Group compared to the Active Group (p = 0.054). Subjects with AC-1 pattern had higher SLEDAI (8.8 ± 7.6) than those with AC-4 (4.8 ± 5.2) (p < 0.001). HEp-2 IFA titer and anti-nuclear antibody by enzyme-linked immunosorbent assay (ANA-ELISA) values were lower in the Remission Group compared to the other two groups (p < 0.001). Multivariate analyses identified only ELISA anti-dsDNA as an independent variable associated with disease activity. In follow-up analysis, HEp-2 IFA titer decreased significantly in the 33 subjects with decreased disease activity (p = 0.002). Receiver operator characteristic (ROC) curve analysis for determination of disease activity showed equivalent areas under the curve (AUC) for HEp-2 IFA titer and traditional disease activity parameters. Conclusions HEp-2 IFA pattern and titer can reflect SLE disease activity and may be considered in conjunction with other laboratory and clinical parameters in the assessment of SLE disease activity.

Practical Utility of D-dimer Test for Venous Thromboembolism in Systemic Lupus Erythematosus Depends on Disease Activity: a Retrospective Cohort Study.

BACKGROUND: The D-dimer test is a screening tool for venous thromboembolism (VTE); however, its utility for patients with systemic lupus erythematosus (SLE) remains unclear. Here, we examined the utility of the D-dimer test as a screening tool for VTE in SLE patients. METHODS: SLE patients (n = 276) and age- and sex-matched patients with non-rheumatic disease (n = 1,104), all of whom underwent D-dimer testing to screen for VTE, were enrolled. The sensitivity and specificity and receiver operating characteristics curve of the D-dimer test were compared in both groups. Then, subgroup of SLE patients in whom the D-dimer test can be useful was sought. RESULTS: The incidence of VTE was more common in SLE patients than controls (10.9% vs. 4.0%). Although the sensitivity of the D-dimer test was comparable between SLE patients and controls (93.3% vs. 90.9%), the specificity of the test was profoundly lower in SLE patients compared to controls (28.4% vs. 84.4%). The area under the curve (AUC) of the D-dimer for VTE was 0.669 in SLE patients and 0.90 in control group. Multiple linear regression analysis demonstrated that SLE disease activity index-2000 (SLEDAI-2K) was significantly associated with D-dimer levels in SLE patients (ß = 0.155; P = 0.022). Subgroup analysis showed that the AUC is moderate (0.768) with low disease activity, while it is low (0.518) with high SLEDAI-2K. CONCLUSION: The D-dimer test may not be a useful screening tool for VTE in patients with active SLE. D-dimer test for predicting VTE in SLE patients should be differentially applied according to disease activity of SLE.

Upregulated fractalkine levels in Chinese patients with lupus nephritis.

OBJECTIVE: To investigate the expression levels of fractalkine (FKN) mRNA in peripheral blood mononuclear cells (PBMCs) and FKN protein in serum of patients with lupus nephritis (LN) from China, and to evaluate the associations between the expression of FKN and systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K), anti-double-stranded DNA and complement proteins in LN patients. METHODS: Real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to detect the expression levels of FKN mRNA in PBMCs and FKN protein in serum separately from 105 patients with LN and 52 healthy controls. RESULTS: Serum level and mRNA level of FKN were significantly increased in LN patients when compared to controls (P < 0.001). Higher FKN levels were found in active LN patients and LN patients with renal damage when compared with inactive LN patients and LN patients without renal damage (P < 0.001). Higher serum FKN levels were detected in inactive LN patients in comparison with healthy controls (Z = -7.165, P < 0.001). The FKN expression levels were positively correlated with SLEDAI-2 K, and was associated with the presence of autoantibodies and negatively correlated with complement proteins C3 and C4 in LN patients. CONCLUSIONS: The results suggest that upregulation of FKN is associated with the pathogenesis and activity of LN in Chinese patients.

Correlation between the Modified Systemic Lupus Erythematosus Disease Activity Index 2000 and the European Consensus Lupus Activity Measurement in juvenile systemic lupus erythematosus.

Objective The objective of this study was to assess Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and European Consensus Lupus Activity Measurement (ECLAM) disease activity correlation in addition to their respective correlation to Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI), in juvenile systemic lupus erythematosus (JSLE). Methods The activity indices were scored retrospectively and summarized by adjusted means during follow-up. The Ped-SDI was scored during the last visit for those with more than six months follow-up. Pearson correlation between the Modified SLEDAI-2K and ECLAM, as well as Spearman correlations between the Modified SLEDAI-2K, ECLAM, and Ped-SDI were calculated. The receiver operating characteristic (ROC) curve was calculated for both activity indices discriminating damage measured by Ped-SDI. Results Thirty-seven patients with mean age at diagnosis 11 ± 2.9 years and mean follow-up time 3.2 ± 2.4 years were studied. The Modified SLEDAI-2K and ECLAM adjusted means were highly correlated ( r = 0.78, p < 0.001). Similarly, Spearman correlation between the activity indices was also high ( rs > 0.7, p < 0.001), but Modified SLEDAI-2K and ECLAM correlation with Ped-SDI was only moderate. ROC analysis discriminant performance for both activity indices resulted in area under curve (AUC) of 0.74 and 0.73 for Modified SLEDAI-2K and ECLAM, respectively. Conclusion The high correlation found between the Modified SLEDAI-2K and ECLAM adjusted means indicated that both tools can be equally useful for longitudinal estimates of JSLE activity.

Treatment of moderately to severely active systemic lupus erythematosus with adrenocorticotropic hormone: a single-site, open-label trial.

BACKGROUND: Alternative therapeutic options are needed for patients with systemic lupus erythematosus (SLE) not adequately controlled with or intolerant to traditional treatments. This study evaluated the efficacy of Acthar® Gel (ACTH(1-39)) for reducing active SLE severity among patients receiving underlying conventional maintenance therapies. METHODS: Ten females (mean age = 49 yrs, disease duration = 7 yrs, Systemic Lupus Erythematosus Disease Activity Index-2000 [SLEDAI-2 K] = 10) currently on maintenance self-administered ACTH(1-39) gel 1 mL (80 U/mL) for 7-15 days and were assessed weekly for 28 days. Outcome measures included Physician and Patient Global Assessments, SLEDAI-2 K, Lupus Quality of Life scale, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, erythrocyte sedimentation rate, and C-reactive protein. Student's t-test compared data obtained at days 7, 14, and 28 with those from baseline. RESULTS: The primary endpoint of SLEDAI-2 K improvement was reached at all observation times (p < 0.05) and statistically significant improvements were observed for most other parameters. No treatment-related serious or unexpected adverse events were observed. CONCLUSIONS: The trial results reveal that among SLE patients in need of therapeutic alternatives, ACTH(1-39) gel may provide significant disease activity reduction.